This application relates to a family of apoptosis modulators that interact with the Huntington's Disease gene product, and to methods and compositions relating thereto.
"Interacting proteins" are proteins which associate in vivo to form specific complexes. Non-covalent bonds, including hydrogen bonds, hydrophobic interactions and other molecular associations form between the proteins when two protein surfaces are matched or have affinity for each other. This affinity or match is required for the recognition of the two proteins, and the formation of an interaction. Protein-protein interactions are involved in the assembly of enzyme subunits; in antigen-antibody reactions; in forming the supramolecular structures of ribosomes, filaments, and viruses; in transport; and in the interaction of receptors on a cell with growth factors and hormones.
Huntington's disease is an adult onset disorder characterized by selective neuronal loss in discrete regions of the brain and spinal chord that lead to progressive movement disorder, personality change and intellectual decline. From onset, which generally occurs around age 40, the disease progresses with worsening symptoms, ending in death approximately 18 years after onset.
The biochemical cause of Huntington's disease is unclear. While the biochemical cause of Huntington's disease has remained elusive, a mutation in a gene within chromosome 4p16.3 subband has been identified and linked to the disease. This gene, referred to as the Huntington's Disease or HD gene, contains two repeat regions, a CAG repeat region and a CCG repeat region. Testing of Huntington's disease patients has shown that the CAG region is highly polymorphic, and that the number of CAG repeat units in the CAG repeat region is a very reliable indicator of having inherited the gene for Huntington's disease. Thus, in control individuals and in most individuals suffering from neuropsychiatric disorders other than Huntington's disease, the number of CAG repeats is between 9 and 35, while in individuals suffering from Huntington's disease the number of CAG repeats is expanded and is 36 or greater.
To date, no differences have been observed at either the total RNA, mRNA or protein levels between normal and HD-affected individuals. Thus, the function of the HD protein and its role in the pathogenesis of Huntington's Disease remain to be elucidated.